title: Cytotoxic effects of gold(III) complexes on established human tumor cell lines sensitive and resistant to cisplatin.
abstract: Gold(III) complexes, isostructural and isoelectronic with platinum(II) complexes, are potentially attractive as anticancer agents. We have synthesized a group of square planar gold(III) complexes, all containing at least two gold-chloride bonds in cis-position, and tested their in vitro cytotoxicity on a panel of established human tumor cell lines. Remarkably, all these compounds showed significant cytotoxic effects. In particular, the complexes containing the salycilaldiminate ligand induced tumor cell growth inhibitory effects comparable to or even greater than cisplatin. All gold(III) complexes substantially retained their antitumor potency against two cisplatin-resistant tumor cell lines (CCRF-CEM/R leukemia and A2780/R ovarian carcinoma); only minimal cross-resistance with cisplatin was observed. When considering the mechanism of action, it is reasonable to assume that the cytotoxicity of these gold(III) complexes derives from DNA binding. Preliminary spectroscopic results are consistent with this hypothesis; indeed, circular dichroism experiments show that both the salycilaldiminate- and the pyridine-containing gold(III) complexes bind calf thymus DNA in vitro and alter reversibly its B-type solution conformation. These results, however, must be treated with caution; solution studies indicate that gold(III) compounds are poorly stable under physiological conditions, possibly implying that, when injected, only a small amount will reach, unchanged, the DNA target. The results of our investigations are discussed in the perspective of future work on the cytotoxic and antitumor properties of gold(III) compounds.
authors.affiliation: Department of Chemistry, University of Florence, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Calamai
authors.forename: S
authors.initials: S
authors.lastname: Carotti
authors.forename: A
authors.initials: A
authors.lastname: Guerri
authors.forename: T
authors.initials: T
authors.lastname: Mazzei
authors.forename: L
authors.initials: L
authors.lastname: Messori
authors.forename: E
authors.initials: E
authors.lastname: Mini
authors.forename: P
authors.initials: P
authors.lastname: Orioli
authors.forename: G P
authors.initials: GP
authors.lastname: Speroni
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry; D018736:DNA Adducts; D019008:Drug Resistance, Neoplasm; D006046:Gold; D006801:Humans; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D013057:Spectrum Analysis; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D018736:DNA Adducts; D009942:Organometallic Compounds; D006046:Gold; D004247:DNA